LOH 19q indicates shorter disease progression-free interval in low-grade oligodendrogliomas with EMP3 methylation

Pasini, Alice; Iorio, Paolo; Bianchi, Emanuela; Cerasoli, Serenella; Cremonini, Anna Maria; Faedi, Marina; Guarnieri, Carlo; Guiducci, Graziano; Riccioni, Luca; Molinari, Chiara; Rengucci, Claudia; Calistri, Daniele; Giordano, Emanuele

doi:10.3892/or.2012.2047

Cited by 10 publications

(9 citation statements)

References 31 publications

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“…It is more frequent in WHO grade II tumors (71.4%) than in WHO grade III tumors (44.7%), in agreement with previous observations [7, 16]. EMP3 promoter hypermethylation is prevalent in oligodendroglial tumors (63%) and in oligoastrocytomas (70%) upon astrocytic tumors (18%), as already reported [5, 7, 8, 13, 14, 16, 17]. Among GBMs, its prevalence in secondary tumors is confirmed [7, 16].…”

Section: Discussionsupporting

confidence: 91%

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Promoter Hypermethylation of theEMP3Gene in a Series of 229 Human Gliomas

Mellai

Piazzi

Caldera

et al. 2013

BioMed Research International

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The epithelial membrane protein 3 (EMP3) is a candidate tumor suppressor gene in the critical region 19q13.3 for several solid tumors, including tumors of the nervous systems. The aim of this study was to investigate the EMP3 promoter hypermethylation status in a series of 229 astrocytic and oligodendroglial tumors and in 16 GBM cell lines. The analysis was performed by methylation-specific PCR and capillary electrophoresis. Furthermore, the EMP3 expression at protein level was evaluated by immunohistochemistry and Western blotting analysis. Associations of EMP3 hypermethylation with total 1p/19q codeletion, MGMT promoter hypermethylation, IDH1/IDH2 and TP53 mutations, and EGFR amplification were studied, as well as its prognostic significance. The EMP3 promoter hypermethylation has been found in 39.5% of gliomas. It prevailed in low-grade tumors, especially in gliomas with an oligodendroglial component, and in sGBMs upon pGBMs. In oligodendroglial tumors, it was strongly associated with both IDH1/IDH2 mutations and total 1p/19q codeletion and inversely with EGFR gene amplification. No association was found with MGMT hypermethylation and TP53 mutations. In the whole series, the EMP3 hypermethylation status correlated with 19q13.3 loss and lack of EMP3 expression at protein level. A favorable prognostic significance on overall survival of the EMP3 promoter hypermethylation was found in patients with oligodendroglial tumors.

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Section: Discussionsupporting

confidence: 91%

“…EMP3 is hypermethylated in 17% of primary GBMs (pGBMs) and in 89% of secondary GBMs (sGBMs), respectively [7]. These observations have been confirmed by other studies [8–17]. Normal nervous tissue showed neither EMP3 hypermethylation nor lack of mRNA expression [10].…”

Section: Introductionsupporting

confidence: 54%

Promoter Hypermethylation of theEMP3Gene in a Series of 229 Human Gliomas

Mellai

Piazzi

Caldera

et al. 2013

BioMed Research International

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“…EMP3 was one of the hub genes in this network. Previous results suggested that EMP3 was a critical biomarker in glioma prognosis [28][29][30][31][32]. EMP was connected with TIMP1 and SERPINE1 and SERPINE1 was connected with IGFBP2 ( Figure 3D).…”

Section: Validation Of Age Related Genes In Glioma Patients Derived Fmentioning

confidence: 65%

“…The prognostic effects of EMP3 [28][29][30][31][32] and IGFBP2 [33][34][35] in glioma patients are extensively studied. Here, we find two EMP3 and IGFBP2 associated genes TIMP1 and SERPINE1 are also suitable biomarkers for prognosis of glioma patients.…”

Section: Discussionmentioning

confidence: 99%

Prognostic significance of age related genes in patients with lower grade glioma

Wang¹,

Wang²,

Xu³

et al. 2020

J. Cancer

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Objective: To analyze the prognostic effects of age in different tumor types and determine the prognostic significance of age related genes in patients with lower grade glioma (LGG). Methods: The relationships between age and tumor overall survival were determined by Kaplan-Meier survival analysis using The Cancer Genome Atlas (TCGA) dataset. The age related genes were identified using TCGA RNA-seq data. Univariate and multivariate cox regression were used to determine the prognostic significance of age related genes. The results derived from TCGA dataset were further validated using Gene Expression Omnibus (GEO) and Chinese Glioma Genome Atlas (CGGA) datasets. Results: Age at initial pathologic diagnosis was most associated with the overall survival of LGG patients than other types of tumor patients. Age related genes EMP3, IGFBP2, TIMP1 and SERPINE1 were highly expressed in old LGG patients. The hypo-methylations of EMP3 and SERPINE1 were contributing to the high expressions of EMP3 and SERPINE1 in old LGG patients. Also, EMP3, IGFBP2, TIMP1 and SERPINE1 were highly expressed in LGG tumor tissues, compared with normal brain tissues. Moreover, high expressions of IGFBP2, EMP3, TIMP1 and SERPINE1 were associated with the worse prognosis of LGG patients. Furthermore, we demonstrated that EMP3 and SERPINE1 were connected with each other and the combination of EMP3 and SERPINE1 had better prognostic effects in glioma patients. Conclusions: Age related genes IGFBP2, EMP3, TIMP1 and SERPINE1 have significant prognostic effects in LGG patients.

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“…EMP3 is a member of the PMP22/EMP/MP20 gene family that plays a role in cell proliferation and cell-cell interactions [27]. Previous studies reported that CpG island hypermethylation in the EMP3 promoter region is frequent in LGGs [28-30]. Moreover, EMP3 promoter hypermethylation is associated with a favorable prognostic significance in OS in patients with oligodendroglial and glioblastoma [29, 31, 32].…”

Section: Discussionmentioning

confidence: 99%

Integrative Analysis of DNA Methylation and Gene Expression Identify a Three-Gene Signature for Predicting Prognosis in Lower-Grade Gliomas

Zeng

Liu

et al. 2018

Cell Physiol Biochem

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Background/Aims: In the current study, we performed an integrated analysis of genome-wide methylation and gene expression data to find novel prognostic genes for lower-grade gliomas (LGGs). Methods: First, TCGA methylation data were used to identify prognostic genes associated with promoter methylation. Second, candidate genes that were stably regulated by promoter methylation were explored. Third, Cox proportional hazards regression analysis was used to generate a prognostic signature, and the signature genes were used to construct a survival risk score system. Results: Three genes (EMP3, GSX2 and EMILIN3) were selected as signature genes. These three signature genes were used to construct a survival risk score system. The high-risk group exhibited significantly worse overall survival (OS) and relapse-free survival (RFS) as compared to the low-risk group in the TCGA dataset. The association of the three-gene prognostic signature with patient’ survival was then validated using the CGGA dataset. Moreover, Kaplan-Meier plots showed that the three-gene prognostic signature risk remarkably stratified grade II and grade III patients in terms of both OS and RFS in the TCGA cohort. There was also a significant difference between the low- and high-risk groups in IDH wild-type glioma patients, indicating that the three-gene signature may be able to help in predicting prognosis for patients with IDH wild-type gliomas. Conclusion: We identified and validated a three-gene (EMP3, GSX2 and EMILIN3) prognostic signature in LGGs by integrating multidimensional genomic data from the TCGA and CGGA datasets, which may help in fine-tuning the current histology-based tumors classification system and providing better stratification for future clinical trials.

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LOH 19q indicates shorter disease progression-free interval in low-grade oligodendrogliomas with EMP3 methylation

Cited by 10 publications

References 31 publications

Promoter Hypermethylation of theEMP3Gene in a Series of 229 Human Gliomas

Promoter Hypermethylation of theEMP3Gene in a Series of 229 Human Gliomas

Prognostic significance of age related genes in patients with lower grade glioma

Integrative Analysis of DNA Methylation and Gene Expression Identify a Three-Gene Signature for Predicting Prognosis in Lower-Grade Gliomas

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